Pulmonary system study

These studies reinforce the stiking biologic and anatomic differences in the several components of the pulmonary system, each with its own potentially unique response (Lippman et al., 1980), and some of the difficulties... 

Krypton-81m has been used to study cardiopulmonary systems from as early as 1970 (X,2). Since then other investigators have proposed its use for myocardial perfusion, (3,4, cerebral perfusion, C5, >), and venography, (.7) A Rb-81 /Kr-81m generator for pulmonary ventilation studies has been commercially available since 1980 from Medi-Physics, Inc. The present work will focus on the manufacture and testing of a Rb-81/Kr-81m generator suitable for liquid elution and use in perfusion studies. 

In an animal, a xenobiotic substance may be bound reversibly to a plasma protein in an inactivated form. A polar xenobiotic substance, or a polar metabolic product, may be excreted from the body in solution in urine. Nonpolar substances delivered to the intestinal tract in bile are eliminated with feces. Volatile nonpolar substances such as carbon monoxide tend to leave the body via the pulmonary system. The ingestion, biotransformation, action on receptor sites, and excretion of a toxic substance may involve complex interactions of biochemical and physiological parameters. The study of these parameters within a framework of metabolism and kinetics is called toxicometrics. 

CN AND CS Toxicity in Animals In animal studies, the cause of death from CN inhalation is the result of toxicity in the pulmonary system. Post-mortem examination from acute toxicity lethality studies in animals... 

Animal studies and human case reports have led to several proposed postexposure prophylactic regimens for asymptomatic patients exposed to pulmonary agents, specifically phosgene, to prevent development of complications. Unfortunately, all of these treatments lack evidence in systemic studies, and asymptomatic patients may find at least one of the treatments unacceptable ... 

Other Organs or Tissues of Potential Metabolic Importance The situation becomes much more complicated when tissues at the body s portals of entry are the focus of drug metabolism studies. Portals of entry include epithelial and other cells in various parts of the gut, cell layers of the skin, and cell linings in different parts of the bronchio-alveolar (pulmonary) system. Problems with these tissues and organs are multifaceted there are usually multiple... 

PFIB primarily affects the pulmonary system. Although animal studies occasionally report disseminated intravascular coagulation and other organ involvement, these effects only occur with sub-... 

It is also important to recognize the portal of entry of nanoparticles when considering human toxicity. Nanoparticles can enter the human body through several different ways. The two most recognized pathways are through the airway or the skin. Since inhalation is the pathway of greatest concern and one of the most studied pathways, the discussion here is focused on inhalation. As nanoparticles have been shown to translocate to other organs (104, 105), not only does inhalation impact the pulmonary system, it can also impact the central nervous system. 

A good description of the particle size properties of an aerosolized drug may give some predictive information on its gross behavior within the tracheobronchial tree. Pulmonary deposition studies will, however, always be necessary to bridge between in vitro measurements and the clinical effect. Therefore, determinations of therapeutic equivalence of different formulations should not rely on in vitro measurements alone. Pharmacokinetic measurements of the systemic absorption are used to evaluate whether two formulations are equivalent. In addition, therapeutic equivalence, pharmacodynamic investigations, and, in some instances, in vivo radiolabel deposition studies should be taken into account (8-10). 

In a subsequent study by the same author, five doses of 4000 pg FLEF were administered at 12-h intervals. The time to reach the peak concentration after each administration ranged from 12.5 to 19.2 min and the fentanyl concentration was maintained within the analgesic therapeutic concentration (0.6-3 ng/mL). The bioavailability of inhaled FLEF is 12-20%, which is consistent with the bioavailability of most drugs administered via the pulmonary system (10-20%). 

Functional evaluations of cardiovascular and pulmonary systems could be incorporated into a non-human primate multi-dose toxicity study. If appropriate, potential reproductive toxicity can be evaluated in a non-human primate. 

The inorganic tin compound that has received the most study from a toxicological viewpoint is stannic oxide. Autopsies performed on workers in the tin mining and refining industry, who inhaled tin oxide dust for as long as 20 yr, disclosed no pulmonary fibrosis (57). Inhalation for long periods produces a benign, symptomless pneumoconiosis with no toxic systemic effects (58). 

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